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31 result(s) for "Dey, Mohan Kumar"
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Biomarkers in Cancer Detection, Diagnosis, and Prognosis
Biomarkers are vital in healthcare as they provide valuable insights into disease diagnosis, prognosis, treatment response, and personalized medicine. They serve as objective indicators, enabling early detection and intervention, leading to improved patient outcomes and reduced costs. Biomarkers also guide treatment decisions by predicting disease outcomes and facilitating individualized treatment plans. They play a role in monitoring disease progression, adjusting treatments, and detecting early signs of recurrence. Furthermore, biomarkers enhance drug development and clinical trials by identifying suitable patients and accelerating the approval process. In this review paper, we described a variety of biomarkers applicable for cancer detection and diagnosis, such as imaging-based diagnosis (CT, SPECT, MRI, and PET), blood-based biomarkers (proteins, genes, mRNA, and peptides), cell imaging-based diagnosis (needle biopsy and CTC), tissue imaging-based diagnosis (IHC), and genetic-based biomarkers (RNAseq, scRNAseq, and spatial transcriptomics).
Three-Dimensional Scaffolds for Bone Tissue Engineering
Immobilization using external or internal splints is a standard and effective procedure to treat minor skeletal fractures. In the case of major skeletal defects caused by extreme trauma, infectious diseases or tumors, the surgical implantation of a bone graft from external sources is required for a complete cure. Practical disadvantages, such as the risk of immune rejection and infection at the implant site, are high in xenografts and allografts. Currently, an autograft from the iliac crest of a patient is considered the “gold standard” method for treating large-scale skeletal defects. However, this method is not an ideal solution due to its limited availability and significant reports of morbidity in the harvest site (30%) as well as the implanted site (5–35%). Tissue-engineered bone grafts aim to create a mechanically strong, biologically viable and degradable bone graft by combining a three-dimensional porous scaffold with osteoblast or progenitor cells. The materials used for such tissue-engineered bone grafts can be broadly divided into ceramic materials (calcium phosphates) and biocompatible/bioactive synthetic polymers. This review summarizes the types of materials used to make scaffolds for cryo-preservable tissue-engineered bone grafts as well as the distinct methods adopted to create the scaffolds, including traditional scaffold fabrication methods (solvent-casting, gas-foaming, electrospinning, thermally induced phase separation) and more recent fabrication methods (fused deposition molding, stereolithography, selective laser sintering, Inkjet 3D printing, laser-assisted bioprinting and 3D bioprinting). This is followed by a short summation of the current osteochondrogenic models along with the required scaffold mechanical properties for in vivo applications. We then present a few results of the effects of freezing and thawing on the structural and mechanical integrity of PLLA scaffolds prepared by the thermally induced phase separation method and conclude this review article by summarizing the current regulatory requirements for tissue-engineered products.
Rheological Characterization and Printability of Sodium Alginate–Gelatin Hydrogel for 3D Cultures and Bioprinting
The development of biocompatible hydrogels for 3D bioprinting is essential for creating functional tissue models and advancing preclinical drug testing. This study investigates the formulation, printability, mechanical properties, and biocompatibility of a novel Alg-Gel hydrogel blend (alginate and gelatin) for use in extrusion-based 3D bioprinting. A range of hydrogel compositions were evaluated for their rheological behavior, including shear-thinning properties, storage modulus, and compressive modulus, which are crucial for maintaining structural integrity during printing and supporting cell viability. The printability assessment of the 7% alginate–8% gelatin hydrogel demonstrated that the 27T tapered needle achieved the highest normalized Printability Index (POInormalized = 1), offering the narrowest strand width (0.56 ± 0.02 mm) and the highest printing accuracy (97.2%) at the lowest printing pressure (30 psi). In contrast, the 30R needle, with the smallest inner diameter (0.152 mm) and highest printing pressure (80 psi), resulted in the widest strand width (0.70 ± 0.01 mm) and the lowest accuracy (88.8%), resulting in a POInormalized of 0.274. The 30T and 27R needles demonstrated moderate performance, with POInormalized values of 0.758 and 0.558, respectively. The optimized 7% alginate and 8% gelatin blend demonstrated favorable printability, mechanical strength, and cell compatibility with MDA-MB-213 breast cancer cells, exhibiting high cell proliferation rates and minimal cytotoxicity over a 2-week culture period. This formulation offers a balanced approach, providing sufficient viscosity for precision printing while minimizing shear stress to preserve cell health. This work lays the groundwork for future advancements in bioprinted cancer models, contributing to the development of more effective tools for drug screening and personalized medicine.
Numerical Study on Sloshing Characteristics with Reynolds Number Variation in a Rectangular Tank
A study on sloshing characteristics in a rectangular tank, which is horizontally excited with a specific range of the Reynolds number, is approached numerically. The nonlinearity of sloshing flow is confirmed by comparing it with the linear solution based on the potential theory, and the time series results of the sloshing pressure are analyzed by Fast Fourier Transform (FFT) algorithm. Then, the pressure fluctuation phenomena are mainly observed and the magnitude of the amplitude spectrum is compared. The results show that, when the impact pressure is generated, large pressure fluctuation in a pressure cycle is observed, and the effects of the frequencies of integral multiples when the fundamental frequency appears dominantly in the sloshing flow.
Creating a retinal image database to develop an automated screening tool for diabetic retinopathy in India
Diabetic retinopathy (DR), a prevalent microvascular complication of diabetes, is the fifth leading cause of blindness worldwide. Given the critical nature of the disease, it is paramount that individuals with diabetes undergo annual screening for early and timely detection of DR, facilitating prompt ophthalmic assessment and intervention. However, screening for DR, which involves assessing visual acuity and retinal examination through ophthalmoscopy or retinal photography, presents a significant global challenge due to the massive volume of individuals requiring annual reviews. To counter this challenge, there has been an increasing interest in the potential of artificial intelligence (AI) tools for automated diagnosis of DR. The AI tools primarily utilize deep learning (DL) techniques and are tailored to analyse extensive medical image data and provide diagnostic outputs, essentially streamline the DR screening process. However, the development of such AI tools requires access to a comprehensive retinal image database with a plethora of high-resolution fundus images from various cameras, covering all DR lesions. Additionally, the accurate training of these AI algorithms necessitates skilled professionals, such as optometrists or ophthalmologists, to provide reliable ground truths that ensure the precision of the diagnostic outputs. To address these prerequisites, we have initiated a study involving multiple institutions to establish a large-scale online 'Retinal Image Database’ in India, aiming to contribute significantly to DR research. This paper delineates the methodology employed for this significant undertaking, detailing the steps taken to create the large retinal image database, as well as the framework for developing a cost-effective, robust AI-based DR diagnostic tool. Our work is expected to mark a significant stride in DR detection and management, promising a more efficient and scalable solution for tackling this global health challenge.
Foxp3+ Regulatory T Cells among Tuberculosis Patients: Impact on Prognosis and Restoration of Antigen Specific IFN-γ Producing T Cells
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) and programmed death-1 (PD-1) molecules have emerged as pivotal players in immune suppression of chronic diseases. However, their impact on the disease severity, therapeutic response and restoration of immune response in human tuberculosis remains unclear. Here, we describe the possible role of Treg cells, their M. tuberculosis driven expansion and contribution of PD-1 pathway to the suppressive function of Treg cells among pulmonary tuberculosis (PTB) patients. Multicolor flow cytometry, cell culture, cells sorting and ELISA were employed to execute the study. Our results showed significant increase in frequency of antigen-reactive Treg cells, which gradually declined during successful therapy and paralleled with decline of M. tuberculosis-specific IL-10 along with elevation of IFN-γ production, and raising the IFN-γ/IL-4 ratio. Interestingly, persistence of Treg cells tightly correlated with MDR tuberculosis. Also, we show that blocking PD-1/PD-L1 pathway abrogates Treg-mediated suppression, suggesting that the PD-1/PD-L1 pathway is required for Treg-mediated suppression of the antigen-specific T cells. Treg cells possibly play a role in dampening the effector immune response and abrogating PD-1 pathway on Treg cells significantly rescued protective T cell response, suggesting its importance in immune restoration among tuberculosis patients.
Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study
18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016. Using all available data sources, the India State-Level Disease Burden Initiative estimated burden (metrics were deaths, disability-adjusted life-years [DALYs], prevalence, incidence, and life expectancy) from 333 disease conditions and injuries and 84 risk factors for each state of India from 1990 to 2016 as part of GBD 2016. We divided the states of India into four epidemiological transition level (ETL) groups on the basis of the ratio of DALYs from communicable, maternal, neonatal, and nutritional diseases (CMNNDs) to those from non-communicable diseases (NCDs) and injuries combined in 2016. We assessed variations in the burden of diseases and risk factors between ETL state groups and between states to inform a more specific health-system response in the states and for India as a whole. DALYs due to NCDs and injuries exceeded those due to CMNNDs in 2003 for India, but this transition had a range of 24 years for the four ETL state groups. The age-standardised DALY rate dropped by 36·2% in India from 1990 to 2016. The numbers of DALYs and DALY rates dropped substantially for most CMNNDs between 1990 and 2016 across all ETL groups, but rates of reduction for CMNNDs were slowest in the low ETL state group. By contrast, numbers of DALYs increased substantially for NCDs in all ETL state groups, and increased significantly for injuries in all ETL state groups except the highest. The all-age prevalence of most leading NCDs increased substantially in India from 1990 to 2016, and a modest decrease was recorded in the age-standardised NCD DALY rates. The major risk factors for NCDs, including high systolic blood pressure, high fasting plasma glucose, high total cholesterol, and high body-mass index, increased from 1990 to 2016, with generally higher levels in higher ETL states; ambient air pollution also increased and was highest in the low ETL group. The incidence rate of the leading causes of injuries also increased from 1990 to 2016. The five leading individual causes of DALYs in India in 2016 were ischaemic heart disease, chronic obstructive pulmonary disease, diarrhoeal diseases, lower respiratory infections, and cerebrovascular disease; and the five leading risk factors for DALYs in 2016 were child and maternal malnutrition, air pollution, dietary risks, high systolic blood pressure, and high fasting plasma glucose. Behind these broad trends many variations existed between the ETL state groups and between states within the ETL groups. Of the ten leading causes of disease burden in India in 2016, five causes had at least a five-times difference between the highest and lowest state-specific DALY rates for individual causes. Per capita disease burden measured as DALY rate has dropped by about a third in India over the past 26 years. However, the magnitude and causes of disease burden and the risk factors vary greatly between the states. The change to dominance of NCDs and injuries over CMNNDs occurred about a quarter century apart in the four ETL state groups. Nevertheless, the burden of some of the leading CMNNDs continues to be very high, especially in the lowest ETL states. This comprehensive mapping of inequalities in disease burden and its causes across the states of India can be a crucial input for more specific health planning for each state as is envisioned by the Government of India's premier think tank, the National Institution for Transforming India, and the National Health Policy 2017. Bill & Melinda Gates Foundation; Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India; and World Bank
Identification of serum sirtuins as novel noninvasive protein markers for frailty
Summary Frailty has emerged as a major health issue among older patients. A consensus on definition and diagnosis is yet to be achieved. Various biochemical abnormalities have been reported in frailty. Activation of sirtuins, a conserved family of NAD‐dependent proteins, is one of the many mimics of calorie restriction which improves lifespan and health in experimental animals. In this cross‐sectional study, we assessed the circulating sirtuin levels in 119 (59.5%) nonfrail and 81 (40.5%) frail individuals, diagnosed by Fried's criteria. Serum SIRT1, SIRT2, and SIRT3 were estimated by surface plasmon resonance (SPR) and Western blot. Serum sirtuins level in mean+SD; SIRT1 (nonfrail –4.67 ± 0.48 ng/μL; frail – 3.72 ± 0.48 ng/μL; P < 0.0001), SIRT2 (nonfrail – 15.18 ± 2.94 ng/μL; frail – 14.19 ± 2.66 ng/μL; P = 0.016), and SIRT3 (nonfrail‐7.72 ± 1.84 ng/μL; frail – 6.12 ± 0.97 ng/μL; P < 0.0001) levels were significantly lower among frail patients compared with the nonfrail. In multivariable regression analysis, lower sirtuins level were significantly associated with frailty after adjusting age, gender, diabetes mellitus, hypertension, cognitive status (Mini Mental State Examination scores) and number of comorbidities. For detecting the optimum diagnostic cutoff value a ROC analysis was carried out. The area under curve for SIRT1 was 0.9037 (cutoff – 4.29 ng/μL; sensitivity – 81.48%; specificity – 79.83%) and SIRT3 was 0.7988 (cutoff – 6.61 ng/μL; sensitivity – 70.37%; specificity – 70.59%). This study shows that lower circulating SIRT1 and SIRT3 levels can be distinctive marker of frailty.
Current Trends of Microfluidic Single-Cell Technologies
The investigation of human disease mechanisms is difficult due to the heterogeneity in gene expression and the physiological state of cells in a given population. In comparison to bulk cell measurements, single-cell measurement technologies can provide a better understanding of the interactions among molecules, organelles, cells, and the microenvironment, which can aid in the development of therapeutics and diagnostic tools. In recent years, single-cell technologies have become increasingly robust and accessible, although limitations exist. In this review, we describe the recent advances in single-cell technologies and their applications in single-cell manipulation, diagnosis, and therapeutics development.